Bottom Line:
Underweight patients are at higher risk of death after acute myocardial infarction (AMI) than normal weight patients; however, it is unclear whether this relationship is explained by confounding due to cachexia or other factors associated with low body mass index (BMI).The adverse effects of low BMI were greatest in patients with very low BMIs.Strategies to promote weight gain in underweight patients after AMI are worthy of testing.

Background: Underweight patients are at higher risk of death after acute myocardial infarction (AMI) than normal weight patients; however, it is unclear whether this relationship is explained by confounding due to cachexia or other factors associated with low body mass index (BMI). This study aimed to answer two questions: (1) does comprehensive risk adjustment for comorbid illness and frailty measures explain the higher mortality after AMI in underweight patients, and (2) is the relationship between underweight and mortality also observed in patients with AMI who are otherwise without significant chronic illness and are presumably free of cachexia?

Methods and findings: We analyzed data from the Cooperative Cardiovascular Project, a cohort-based study of Medicare beneficiaries hospitalized for AMI between January 1994 and February 1996 with 17 y of follow-up and detailed clinical information to compare short- and long-term mortality in underweight and normal weight patients (n = 57,574). We used Cox proportional hazards regression to investigate the association of low BMI with 30-d, 1-y, 5-y, and 17-y mortality after AMI while adjusting for patient comorbidities, frailty measures, and laboratory markers of nutritional status. We also repeated the analyses in a subset of patients without significant comorbidity or frailty. Of the 57,574 patients with AMI included in this cohort, 5,678 (9.8%) were underweight and 51,896 (90.2%) were normal weight at baseline. Underweight patients were older, on average, than normal weight patients and had a higher prevalence of most comorbidities and measures of frailty. Crude mortality was significantly higher for underweight patients than normal weight patients at 30 d (25.2% versus 16.4%, p < 0.001), 1 y (51.3% versus 33.8%, p < 0.001), 5 y (79.2% versus 59.4%, p < 0.001), and 17 y (98.3% versus 94.0%, p < 0.001). After adjustment, underweight patients had a 13% higher risk of 30-d death and a 26% higher risk of 17-y death than normal weight patients (30-d hazard ratio [HR] 1.13, 95% CI 1.07-1.20; 17-y HR 1.26, 95% CI 1.23-1.30). Survival curves for underweight and normal weight patients separated early and remained separate over 17 y, suggesting that underweight patients remained at a significant survival disadvantage over time. Similar findings were observed among the subset of patients without comorbidity at baseline. Underweight patients without comorbidity had a 30-d adjusted mortality similar to that of normal weight patients but a 21% higher risk of death over the long term (30-d HR 1.08, 95% CI 0.93-1.26; 17-y HR 1.21, 95% CI 1.14-1.29). The adverse effects of low BMI were greatest in patients with very low BMIs. The major limitation of this study was the use of surrogate markers of frailty and comorbid conditions to identify patients at highest risk for cachexia rather than clear diagnostic criteria for cachexia.

Conclusions: Underweight BMI is an important risk factor for mortality after AMI, independent of confounding by comorbidities, frailty measures, and laboratory markers of nutritional status. Strategies to promote weight gain in underweight patients after AMI are worthy of testing.

pmed.1001998.g001: Kaplan–Meier survival curves for underweight and normal weight among allpatients and the subset of patients without significant comorbidity orfrailty.Curves for (A) all patients and (B) the subset of patients withoutsignificant comorbidity or frailty. The lines represent the Kaplan–Meiersurvivor functions, and the shaded areas are the 95% confidence limits.p-Value for log-rank test < 0.001 for bothcomparisons.

Mentions:
In-hospital mortality was significantly higher for underweight patients compared withnormal weight patients; however, rates of most other in-hospital complications weresimilar (Table 1). Crudemortality was significantly higher for underweight patients than normal weightpatients at 30 d (25.2% versus 16.4%), 1 y (51.3% versus 33.8%), 5 y (79.2% versus59.4%), and 17 y (98.3% versus 94.0%) (all p < 0.001) (Fig 1; Table 1). Conditional HRs showed divergence ofthe survival curves over all 17 y of follow-up, suggesting that underweight patientsremained at a significant survival disadvantage over time (Table 2). After adjustment for patient andtreatment characteristics during the index admission, underweight patients remainedat a significant survival disadvantage across all follow-up time points: the curvesdiverged early and remained separate over the 17 y of follow-up. Underweightpatients had a 13% greater risk of death within the first 30 d and a 26% greaterrisk of death over the full 17 y of follow-up (30-d adjusted HR 1.13, 95% CI1.07–1.20; 17-y adjusted HR 1.26, 95% CI 1.23–1.30) (Table 2).

pmed.1001998.g001: Kaplan–Meier survival curves for underweight and normal weight among allpatients and the subset of patients without significant comorbidity orfrailty.Curves for (A) all patients and (B) the subset of patients withoutsignificant comorbidity or frailty. The lines represent the Kaplan–Meiersurvivor functions, and the shaded areas are the 95% confidence limits.p-Value for log-rank test < 0.001 for bothcomparisons.

Mentions:
In-hospital mortality was significantly higher for underweight patients compared withnormal weight patients; however, rates of most other in-hospital complications weresimilar (Table 1). Crudemortality was significantly higher for underweight patients than normal weightpatients at 30 d (25.2% versus 16.4%), 1 y (51.3% versus 33.8%), 5 y (79.2% versus59.4%), and 17 y (98.3% versus 94.0%) (all p < 0.001) (Fig 1; Table 1). Conditional HRs showed divergence ofthe survival curves over all 17 y of follow-up, suggesting that underweight patientsremained at a significant survival disadvantage over time (Table 2). After adjustment for patient andtreatment characteristics during the index admission, underweight patients remainedat a significant survival disadvantage across all follow-up time points: the curvesdiverged early and remained separate over the 17 y of follow-up. Underweightpatients had a 13% greater risk of death within the first 30 d and a 26% greaterrisk of death over the full 17 y of follow-up (30-d adjusted HR 1.13, 95% CI1.07–1.20; 17-y adjusted HR 1.26, 95% CI 1.23–1.30) (Table 2).

Bottom Line:
Underweight patients are at higher risk of death after acute myocardial infarction (AMI) than normal weight patients; however, it is unclear whether this relationship is explained by confounding due to cachexia or other factors associated with low body mass index (BMI).The adverse effects of low BMI were greatest in patients with very low BMIs.Strategies to promote weight gain in underweight patients after AMI are worthy of testing.

Background: Underweight patients are at higher risk of death after acute myocardial infarction (AMI) than normal weight patients; however, it is unclear whether this relationship is explained by confounding due to cachexia or other factors associated with low body mass index (BMI). This study aimed to answer two questions: (1) does comprehensive risk adjustment for comorbid illness and frailty measures explain the higher mortality after AMI in underweight patients, and (2) is the relationship between underweight and mortality also observed in patients with AMI who are otherwise without significant chronic illness and are presumably free of cachexia?

Methods and findings: We analyzed data from the Cooperative Cardiovascular Project, a cohort-based study of Medicare beneficiaries hospitalized for AMI between January 1994 and February 1996 with 17 y of follow-up and detailed clinical information to compare short- and long-term mortality in underweight and normal weight patients (n = 57,574). We used Cox proportional hazards regression to investigate the association of low BMI with 30-d, 1-y, 5-y, and 17-y mortality after AMI while adjusting for patient comorbidities, frailty measures, and laboratory markers of nutritional status. We also repeated the analyses in a subset of patients without significant comorbidity or frailty. Of the 57,574 patients with AMI included in this cohort, 5,678 (9.8%) were underweight and 51,896 (90.2%) were normal weight at baseline. Underweight patients were older, on average, than normal weight patients and had a higher prevalence of most comorbidities and measures of frailty. Crude mortality was significantly higher for underweight patients than normal weight patients at 30 d (25.2% versus 16.4%, p < 0.001), 1 y (51.3% versus 33.8%, p < 0.001), 5 y (79.2% versus 59.4%, p < 0.001), and 17 y (98.3% versus 94.0%, p < 0.001). After adjustment, underweight patients had a 13% higher risk of 30-d death and a 26% higher risk of 17-y death than normal weight patients (30-d hazard ratio [HR] 1.13, 95% CI 1.07-1.20; 17-y HR 1.26, 95% CI 1.23-1.30). Survival curves for underweight and normal weight patients separated early and remained separate over 17 y, suggesting that underweight patients remained at a significant survival disadvantage over time. Similar findings were observed among the subset of patients without comorbidity at baseline. Underweight patients without comorbidity had a 30-d adjusted mortality similar to that of normal weight patients but a 21% higher risk of death over the long term (30-d HR 1.08, 95% CI 0.93-1.26; 17-y HR 1.21, 95% CI 1.14-1.29). The adverse effects of low BMI were greatest in patients with very low BMIs. The major limitation of this study was the use of surrogate markers of frailty and comorbid conditions to identify patients at highest risk for cachexia rather than clear diagnostic criteria for cachexia.

Conclusions: Underweight BMI is an important risk factor for mortality after AMI, independent of confounding by comorbidities, frailty measures, and laboratory markers of nutritional status. Strategies to promote weight gain in underweight patients after AMI are worthy of testing.